COMMODITIES Trial: Initial Dual Oral Therapy vs Monotherapy in PAH With Cardiovascular Comorbidities

Exclusion Criteria

• •Porto-pulmonary hypertension
• •Uncorrected systemic-to-pulmonary congenital shunt
• •Evidence of thromboembolic disease assessed by ventilation perfusion (V/Q) lung scan or CT pulmonary angiography
• •Patients listed for lung or heart-lung transplantation at time of screening
• •Patients on any PAH-specific drug therapy at any time preceding randomisation
• •Known moderate-to-severe restrictive lung disease (i.e., total lung capacity \< 60% of predicted value) or obstructive lung disease (i.e., forced expiratory volume in one second \[FEV1\] \< 60% of predicted, with FEV1 / forced vital capacity \< 65%) or known significant chronic lung disease diagnosed by chest imaging (e.g., interstitial lung disease, emphysema).
• •Known or suspected pulmonary veno-occlusive disease (PVOD)
• •Severe renal insufficiency (creatinine clearance \< 30 mL/min)
• •Documented severe hepatic impairment (with or without cirrhosis) according to National Cancer Institute organ dysfunction working group criteria, defined as total bilirubin \> 3 x ULN or serum AST and/or ALT \> 3xULN (assessed by local laboratory at screening) and/or Child-Pugh Class C.
• •Haemoglobin \< 10 g/dL
• •Patient under guardianship curatorship, deprived of liberty
• •Pregnant women, or breast-feeding women
• •Treatment with other PDE-5i for erectile dysfunction
• •Ongoing or planned treatment with nitrates and/or doxazosin.
• •Ongoing or planned treatment with riociguat
• •Treatment with strong inducers of CYP3A4 (e.g., carbamazepine, rifampin, rifampicin, rifabutin, rifapentin, phenobarbital, phenytoin, and St. John's wort) ≤28 days preceding randomisation